The compound of formula (I): ##STR2## has two optically-active or "chiral" centers, i.e., at the 1' and 4' positions, each of which can exhibit an "R" or an "S" stereo configuration. As will be appreciated by those skilled in this art, a molecule of the compound of formula (I) exists as one of four possible isomers. The concept of stereo configuration and the associated conventions of stereochemistry are explained in essentially all standard tests on organic chemistry, for example, see Mar., J., Advanced Organic Chemistry, 3d. Ed., Chap. 4, John Wiley & Sons, N.Y. (1985).
In the compound of formula (I), there are two isomeric pairs each consisting of two enantiomers (isomers which are mirror images of each other). The isomeric pairs are referred to as either "cis" (same side) or "trans" (opposite sides) with respect to the relationship of the non-hydrogen ring substituents attached to the chiral centers. The isomers may be named by specifying the absolute configuration at each chiral center, e.g., 1R, 4S, or prefixing the compound name with the absolute configuration of one of the chiral centers followed by the "cis" or "trans" designation, i.e., 1R-cis, 1R-trans, 1S-cis and 1S-trans.
The cis form of formula (I) is depicted below as formula (II): ##STR3## and is meant to represent both cis enantiomers. Thus, the convention of both the 1' and 4' bonds being bold faced is meant to include the enantiomers where the bonds are cis, whether out of the plane of the page or into it. The racemic mixture (equal mixture) of both the 1R-cis and 1S-cis enantiomers of the compound of formula (II) is known as carbovir or (+/-)-carbovir. While racemic carbovir has been reported as having good activity against human immunodeficiency virus (HIV) associated with acquired immune deficiency syndrome (AIDS), the 1R-cis enantiomer of carbovir, also known as (-)-carbovir, (hereinafter these terms are used interchangeably) has been found to have potent activity against this virus (see Vince, R., et al, Biochem. Biophys. Res. Commun., 156 (2), 1046 (1988). In view of the high activity of the 1R-cis enantiomer, it is particularly advantageous to have an efficient method for the synthesis of this enantiomer from relatively inexpensive starting materials.
In view of its guanine moiety, (-)-carbovir exist in two tautomeric forms. For simplicity, herein (-)-carbovir is depicted in the keto form as shown in formula (II), it being understood that it also is represented as the enol form in some publications. ##STR4##